Pathophysiology and etiology of achalasia
- Stuart J Spechler, MD
Stuart J Spechler, MD
- Berta M and Cecil O Patterson Professor of Medicine
- University of Texas Southwestern Medical Center at Dallas
The act of swallowing (deglutition) normally initiates a peristaltic wave that propels ingested material down the esophagus. Deglutition also triggers relaxation of the lower esophageal sphincter (LES), a process that allows the swallowed material to enter the stomach.
Achalasia (a Greek term that means "does not relax") is a disease of unknown cause in which there is a loss of peristalsis in the distal esophagus (whose musculature is comprised predominantly of smooth muscle) and a failure of LES relaxation. Although both of these abnormalities impair esophageal emptying, the symptoms of achalasia (eg, dysphagia and regurgitation) are due primarily to the defect in LES relaxation. The relentless LES contraction in achalasia causes functional obstruction of the esophagus (picture 1) that persists until the hydrostatic pressure of the retained material exceeds the pressure generated by the sphincter muscle.
The pathophysiology and etiology of achalasia will be reviewed here. The clinical manifestations, diagnosis, and treatment of this disorder are discussed separately. (See "Achalasia: Pathogenesis, clinical manifestations, and diagnosis" and "Overview of the treatment of achalasia".)
Achalasia results from the degeneration of neurons in the esophageal wall (figure 1) . Histologic examination reveals decreased numbers of neurons (ganglion cells) in the myenteric plexuses, and the ganglion cells that remain often are surrounded by lymphocytes and, less prominently, by eosinophils [2,3]. This inflammatory degeneration preferentially involves the nitric oxide-producing, inhibitory neurons that effect the relaxation of esophageal smooth muscle; the cholinergic neurons that contribute to lower esophageal sphincter (LES) tone by causing smooth muscle contraction may be relatively spared .
In some patients, degenerative changes are also found in the ganglion cells of the dorsal motor nucleus of the vagus in the brainstem, and Wallerian degeneration has been observed in the vagal fibers that supply the esophagus (figure 1) . However, the disordered motility that characterizes achalasia appears to result primarily from the loss of inhibitory neurons within the wall of the esophagus itself. Loss of inhibitory innervation in the LES causes the basal sphincter pressure to rise, and renders the sphincter muscle incapable of normal relaxation. In the smooth muscle portion of the esophageal body, the loss of inhibitory neurons results in aperistalsis.
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